Bench to bedside defining calcific aortic valve disease: osteocardiology

Rajamannan, Nalini M.; Moura, Luís M; Best, Patricia J.M.

doi:10.1080/14779072.2020.1757431

Cited by 3 publications

(2 citation statements)

References 72 publications

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“…The calcific aortic valve disease (CAVD) resides among the world’s most prevalent culprits of cardiovascular disorders [ 1 , 2 , 75 ]. There is an implicit need of profound investigation, especially because of lacking conservative treatment options [ 1 , 45 ]. Thorough understanding of the multifactorial pathophysiological processes underlying CAVD may provide novel prophylactic strategies for people at risk as well as curative treatment options for patients already suffering CAVD.…”

Section: Discussionmentioning

confidence: 99%

“…Limitation of calcification in contrary is possible by adding pro-calcifying or osteogenic media [ 79 – 81 ]. More realistic representation was achieved using animal models but altered microanatomy and absent/reduced calcification potential limited model applicability [ 9 , 15 , 26 – 29 , 31 , 32 , 45 ]. Pro-calcifying or osteogenic substance-based induction is not possible in animals but spontaneous AV calcification could be at most observed in porcine samples, accelerated by supplying high cholesterol and fat diet [ 28 , 82 – 84 ].…”

Section: Discussionmentioning

confidence: 99%

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Challenges of aortic valve tissue culture – maintenance of viability and extracellular matrix in the pulsatile dynamic microphysiological system

Dittfeld,

Winkelkotte,

Scheer

et al. 2023

J Biol Eng

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Background Calcific aortic valve disease (CAVD) causes an increasing health burden in the 21st century due to aging population. The complex pathophysiology remains to be understood to develop novel prevention and treatment strategies. Microphysiological systems (MPSs), also known as organ-on-chip or lab-on-a-chip systems, proved promising in bridging in vitro and in vivo approaches by applying integer AV tissue and modelling biomechanical microenvironment. This study introduces a novel MPS comprising different micropumps in conjunction with a tissue-incubation-chamber (TIC) for long-term porcine and human AV incubation (pAV, hAV). Results Tissue cultures in two different MPS setups were compared and validated by a bimodal viability analysis and extracellular matrix transformation assessment. The MPS-TIC conjunction proved applicable for incubation periods of 14–26 days. An increased metabolic rate was detected for pulsatile dynamic MPS culture compared to static condition indicated by increased LDH intensity. ECM changes such as an increase of collagen fibre content in line with tissue contraction and mass reduction, also observed in early CAVD, were detected in MPS-TIC culture, as well as an increase of collagen fibre content. Glycosaminoglycans remained stable, no significant alterations of α-SMA or CD31 epitopes and no accumulation of calciumhydroxyapatite were observed after 14 days of incubation. Conclusions The presented ex vivo MPS allows long-term AV tissue incubation and will be adopted for future investigation of CAVD pathophysiology, also implementing human tissues. The bimodal viability assessment and ECM analyses approve reliability of ex vivo CAVD investigation and comparability of parallel tissue segments with different treatment strategies regarding the AV (patho)physiology.

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Section: Discussionmentioning

confidence: 99%